Low-density lipoprotein receptor-related protein 4 (LRP4)

Low-density lipoprotein receptor-related protein 4 (LRP4) is a single-pass transmembrane receptor belonging to the LDL receptor family[4][1]. It contains multiple extracellular EGF-like, LDLa, and β-propeller domains that mediate its interactions with extracellular ligands including agrin, MuSK, Wnt antagonists (SOST, Wise, Dkk1)[3][6]. At the neuromuscular junction, LRP4 is required for both postsynaptic differentiation and presynaptic organization by acting as a coreceptor/clamp that stabilizes agrin-MuSK complexes[3][6][1]. LRP4 also modulates Wnt/β-catenin signaling independently and through partners like SOST, with roles in development and tissue homeostasis[1][4][6]. Clinically, LRP4 is implicated as an autoimmune target in a subset of myasthenia gravis patients, and anti-LRP4 antibodies correlate with more severe disease presentation[2][5]. There is significant interest in LRP4 for both mechanistic research and therapeutic targeting in synaptic biology, neurodevelopment, and autoimmunity.

Other names

LRP4KIAA0816LRP-4MEGF7CLSSSOST2CMS17LRP10multiple EGF-like domains 7Multiple epidermal growth factor-like domains 7

Inhibition of autoantibody activity (immunomodulators, plasmapheresis, IVIg); Acetylcholinesterase inhibition (e.g., pyridostigmine increases acetylcholine signaling when AChR function is impaired); Immunosuppression (prednisone, azathioprine), reducing antibody-mediated pathology.